The use of therapeutic binding proteins has revolutionized the treatment of many diseases, including cancer, inflammatory bowel disease (IBD), ankylosing spondylitis, multiple sclerosis, psoriasis and rheumatoid arthritis (RA). Despite their success in improving the quality of life of patients, long-term treatment with therapeutic binding proteins is often associated with the emergence of anti-drug antibodies (ADA) against the therapeutic agent. The development of ADA results in progressively lower serum drug levels and a diminished treatment efficacy.
For example, a 2011 study of rheumatoid arthritis patients treated with adalimumab revealed the development of anti-drug antibodies resulted in significantly lower remission rates. Two-thirds of the anti-adalimumab antibody-positive patients developed antibodies to the drug within the first 28 weeks of treatment. The presence of anti-adalimumab antibodies was further shown to substantially reduce serum adalimumab concentrations Similar results have been reported for infliximab, adalimumab, and natalizumab (see Bartelds et al., JAMA. 2011; 305(14):1460-1468). Such ADA immune responses, therefore, decrease the overall efficacy and utility of therapeutic binding proteins.
Accordingly, there is a need in the art for recombinant protein therapeutics compositions that exhibit a reduced ADA response relative to current therapeutic binding proteins.